We use U-Th/(He) zircon and apatite thermochronology and Al in hornblende geobarometry from Eocene granitoids of the Sierra Nevada de Santa Marta and Guajira uplifted massifs in northern Colombia to elucidate the exhumation history of the northern South America continental margin and its bearing to Cenozoic Caribbean- South American plate interactions. Aluminium in hornblende geobarometry from the Eocene Santa Marta batholith yields pressures between 4.9±0.6kbar and 6.4±0.6kbar, which indicate that at least, 14.7-19.2km of unroofing took place since 56-50Ma in the northwestern Sierra Nevada de Santa Marta. In the Guajira Peninsula, calculated pressures for the Eocene Parashi stock are 2.3±0.6kbar and 3±0.6kbar. Stratigraphic considerations pertaining to Oligocene conglomerates from the Guajira area suggest that 6.9-9km of crust was lost between 50Ma and ca. 26Ma. U-Th/He zircon and apatite thermochronology from granitoids in the Sierra Nevada de Santa Marta shows the existence of major exhumation events in the Late Eocene (ca. 45-40Ma), Late Oligocene (ca. 25Ma) and Miocene (ca. 15Ma). The Guajira region records the Late Eocene to Early Oligocene (35-25Ma) event, but it lacks evidence for the Miocene exhumation phase. These differences reflect isolation of the Guajira region from the Sierra Nevada de Santa Marta and the Andean chain due to extensive block rotation and transtensional tectonics that affected the region during post-Eocene times. The post-Eocene events correlate in time with an increased convergence rate and the frontal approach of North and South America. It is suggested that the two major tectonic mechanisms that govern exhumation in these Caribbean massifs are: 1) subduction of the Caribbean plate, and 2) post Eocene changes in plate convergence obliquity and rates that caused the South American continental margin blocks to override the Caribbean plate. Temporal correlation with other Caribbean and Northern Andean events allows to resolve the regional Cenozoic plate tectonic reorganizations experienced by the South American, Caribbean and Pacific plates at a regional scale.